There is a hypothesis that hyperinsulinemia or insulin resistance may be a mediator for breast cancer risk factors. On the other hand, some but not all of the well-known risk factors of breast cancer have been associated with serum estrogen concentrations. We assessed the relationships of potential breast cancer risk factors to indicators of insulin resistance, fasting plasma insulin concentration and homeostasis model assessment insulin resistance (HOMA-R), in 88 postmenopausal Japanese women. We also examined whether insulin resistance would explain the association of breast cancer risk factors with serum estradiol and sex hormone-binding globulin (SHBG). Information on potential breast cancer risk factors such as demographic characteristics, smoking and drinking habits, diet, exercise, menstrual and reproductive factors were obtained by self-administered health questionnaire including validated semiquantitative food frequency questionnaire. Body mass index (BMI) was significantly correlated with the ratio of estradiol to SHBG, fasting plasma insulin, and HOMA-R after controlling for age. The correlations were still significant between BMI and estradiol/SHBG ratio after controlling for fasting plasma insulin and between BMI and fasting plasma insulin as well as HOMA-R after controlling for estradiol/SHBG ratio. There is a possibility that effect of BMI on breast cancer risk is mediated by both insulin resistance and estrogen metabolism.